The present invention includes monomer compositions containing aspartic acid and other comonomers, such as monosodium aspartate, and methods for their production. The monomer compositions can be polymerized, particularly by thermal polymerization, to obtain useful and novel imide-containing polyamino acids, i.e., copolymers containing polymerized aspartic acid or aspartate units and succinimide units. Thus, the invention is also directed to the resulting polymeric materials, their methods of production, and their uses as described herein. Uses of the imide-containing polyamino acids include, for example, dispersants in detergents and cleaners, water-treatment chemicals as anti-scalants and corrosion inhibitors, personal-care additives for softening and moisturizing, and many others.
Aspartic acid has been produced commercially since the 1980""s via immobilized enzyme methods. The aspartic acid so produced mainly has been used as a component of the synthetic sweetener, N-aspartyl phenylalanine methyl ester (ASPARTAME(copyright)).
In a typical production pathway, a solution of ammonium maleate is converted to fumarate via action of an immobilized enzyme, maleate isomerase, by continuous flow over an immobilized enzyme bed. Next, the solution of ammonium fumarate is treated also by continuous flow of the solution over a bed of the immobilized enzyme, aspartase. A relatively concentrated solution of ammonium asparate is produced, which then is treated with an acid, for example nitric acid, to precipitate aspartic acid. After drying, the resultant product of the process is powdered or crystalline L-aspartic acid. Prior art that exemplifies this production pathway includes U.S. Pat. No. 4,560,653 to Sherwin and Blouin (1985), U.S. Pat. No. 5,541,090 to Sakano et al. (1996), and U.S. Pat. No. 5,741,681 to Kato et al. (1998).
In addition, nonenzymatic, chemical routes to D,L aspartic acid via treatment of maleic acid, fumaric acid, or their mixtures with ammonia at elevated temperature have been known for over 150 years (see Harada, K., Polycondensation of thermal precursors of aspartic acid. Journal of Organic Chemistry 24, 1662-1666 (1959); also, U.S. Pat. No. 5,872,285 to Mazo et al. (1999)). Although the nonenzymatic routines are significantly less quantitative than the enzymatic syntheses of aspartic acid, possibilities of continuous processes and recycling of reactants and by-products via chemical routes are envisioned.
Polymerization and copolymerization of aspartic acid alone or with other comonomers is known. As reviewed in U.S. Pat. No. 5,981,691 to Sikes (1999), synthetic work with polyamino acids, beginning with the homopolymer of aspartic acid, dates to the mid 1800""s and has continued to the present. Interest in polyaspartates and related molecules increased in the mid 1980""s as awareness of the commercial potential of these molecules grew. Particular attention has been paid to biodegradable and environmentally compatible polyaspartates for commodity uses such as detergent additives and superabsorbent materials in disposable diapers, although numerous other uses have been contemplated, ranging from water-treatment additives for control of scale and corrosion to anti-tartar agents in toothpastes.
There have been some teachings of producing copolymers of succinimide and aspartic acid or aspartate via thermal polymerization of maleic acid plus ammonia or ammonia compounds. For example, U.S. Pat. No. 5,548,036 to Kroner et al. (1996) taught that polymerization at less than 140xc2x0 C. resulted in aspartic acid residue-containing polysuccinimides. However, the reason that some aspartic acid residues persisted in the product polymers was that the temperatures of polymerization were too low to drive the reaction to completion, leading to inefficient processes.
JP 8277329 (1996) to Tomida exemplified the thermal polymerization of potassium asparate in the presence of 5 mol % and 30 mole % phosphoric acid. The purpose of the phosphoric acid was stated to serve as a catalyst so that molecules of higher molecular weight might be produced. However, the products of the reaction were of a lower molecular weight than were produced in the absence of the phosphoric acid, indicating that there was no catalytic effect. There was no mention of producing copolymers of aspartate and succinimide; rather, there was mention of producing only homopolymers of polyaspartate. In fact, addition of phosphoric acid in this fashion to form a slurry or intimate mixture with the powder of potassium aspartate, is actually counterproductive to formation of copolymers containing succinimide and aspartic acid residue units, or to formation of the condensation amide bonds of the polymers in general. That is, although the phosphoric acid may act to generate some fraction of residues as aspartic acid, it also results in the occurrence of substantial amounts of phosphate anion in the slurry of mixture. Upon drying to form the salt of the intimate mixture, such anions bind ionically with the positively charged amine groups of aspartic acid and aspartate residues, blocking them from the polymerization reaction, thus resulting in polymers of lower molecular weight in lower yield.
Earlier, U.S. Pat. No. 5,371,180 to Groth et al. (1994) had demonstrated production of copolymers of succinimide and aspartate by thermal treatment of maleic acid plus ammonium compounds in the presence of alkaline carbonates. The invention involved an alkaline, ring-opening environment of polymerization such that some of the polymeric succinimide residues would be converted to the ring-opened, aspartate form. For this reason, only alkaline carbonates were taught and there was no mention of cations functioning themselves in any way to prevent imide formation.
More recently, U.S. Pat. No. 5,936,121 to Gelosa et al. (1999) taught formation of oligomers (Mw less than 1000) of aspartate having chain-terminating residues of unsaturated dicarboxylic compounds such as maleic and acrylic acids. These aspartic-rich compounds were formed via thermal condensation of mixtures of sodium salts of maleic acid plus ammonium/sodium maleic salts that were dried from solutions of ammonium maleate to which NaOH had been added. They were producing compounds to sequester alkaline-earth metals. In addition, the compounds were shown to be nontoxic and biodegradable by virtue of their aspartic acid composition. Moreover, the compounds retained their biodegradability by virtue of their very low Mw, notwithstanding the presence of the chain-terminating residues, which when polymerized with themselves to sizes about the oligomeric size, resulted in non-degradable polymers.
A number of reports and patents in the area of polyaspartics (i.e., poly(aspartic acid) or polyaspartate), polysuccinimides, and their derivatives have appeared more recently. Notable among these, for example, there have been disclosures of novel superabsorbents (U.S. Pat. No. 5,955,549 to Chang and Swift, 1999; U.S. Pat. No. 6,027,804 to Chou et al., 2000), dye-leveling agents for textiles (U.S. Pat. No. 5,902,357 to Riegels et al., 1999), and solvent-free synthesis of sulfhydryl-containing corrosion and scale inhibitors (EP 0 980 883 to Oda, 2000). There also has been teaching of dye-transfer inhibitors prepared by nucleophilic addition of amino compounds to polysuccinimide suspended in water (U.S. Pat. No. 5,639,832 to Kroner et al., 1997), which reactions are inefficient due to the marked insolubility of polysuccinimide in water.
U.S. Pat. No. 5,981,691 purportedly introduced the concept of mixed amide-imide, water-soluble copolymers of aspartate and succinimide for a variety of uses. The concept therein was that a monocationic salt of aspartate when formed into a dry mixture with aspartic acid could be thermally polymerized to produce the water-soluble copoly(aspartate, succinimide). The theory was that the aspartic acid comonomer when polymerized led to succinimide residues in the product polymer and the monosodium aspartate comonomer led to aspartate residues in the product polymer. It was not recognized that merely providing the comonomers was not sufficient to obtain true copolymers and that certain other conditions were necessary to avoid obtaining primarily mixtures of polyaspartate and polysuccinimide copolymers. In U.S. Pat. No. 5,981,691, the comonomeric mixtures were formed from an aqueous slurry of aspartic acid, adjusted to specific values of pH, followed by drying. There was no teaching of use of solutions of ammonium aspartate or any other decomposable cation plus NaOH, or other forms of sodium or other cations, for generation of comonomeric compositions of aspartic acid and salts of aspartate. Thus, although some of the U.S. Pat. No. 5,981,691 examples obtain products containing some copolymer in mixture with other products, particularly homopolymers, as discussed in the Summary of the Invention below, the theory that true copolymers could be obtained merely by providing the comonomers in the manner taught in U.S. Pat. No. 5,981,691 was not fully realized.
Thus, to date, there have been no successful disclosures of water-soluble or wettable, mixed amide/imide polyamino acids such as copolymers of aspartate and succinimide or related imide-containing polyamino acids.
It has now been discovered that the methods taught in U.S. Pat. No. 5,981,691, or in any of the other discussed references, fail to provide an efficient process to produce a true mixed amide/imide polyamino acid copolymer, a copolymer prepared by such process or other novel copolymers. These previous references fail to teach a method whereby a sufficiently intimate mixture of the comonomers is provided such that polymerization leads to a true copolymer with a significant number of both aspartate and succinimide residues. For example, the above-described method of U.S. Pat. No. 5,981,691 purportedly for producing such copolymers results, instead in a mixture, albeit intimate mixture, of aspartic acid (amide and succinimide (imide) homopolymers, possibly with an amount of copolymer, unappreciated by the reference, mixed therein. A method has now been discovered providing a sufficiently intimate mixture of the comonomers and, therefore, allowing the production of a true copolymer with a significant number of both aspartate (also referred to as amide) residues or units and succinimide (also referred to as imide) units or residues, as schematically show by the following formula. 
The invention also can provide the resulting copolymers in isolated form. By isolated form it is meant that the copolymer is either: (a) in the substantial absence, e.g., less than 10%, preferably less than 5%, more particularly less than 1%, by weight of a polyaspartate or polysuccinimide homopolymer, (b) prepared by a method defined by this invention or (c) polyaspartate and/or polysuccinimide homopolymer from the copolymer.
Accordingly, the present invention teaches novel methods for producing mixed amide/imide copolymers of amino acids, as well as the resulting novel imide-containing polyamino acids themselves. Included are methods employing the monomers aspartic acid or aspartate salts having non-volatile or non-heat-decomposable cations. By aspartate or aspartate salt is meant a salt of the aspartate ion and any metallic cation, including alkali metal, alkaline earth metals or transition metals. Preferably the cations are alkali or alkaline earth metals, particularly Na, Mg, K, Ca, Rb, Sr, Cs and Ba, with sodium, magnesium, potassium and calcium, particularly sodium, being preferred. These monomers lead to amide formation. Other monomer, particularly aspartates having a volatile or heat-decomposable cation, preferably an ammonium or amine cation, lead to imide formation. In the following, the amide-generating cation will be represented by sodium (Na+) and the imide-generating cation will be represented by ammonium (NH4+) but with the understanding that other cations creating the same effects for achieving the invention may be substituted. By volatile or heat-decomposable cation it is meant that the cation sufficiently dissociates from the aspartate anion under the giving drying conditions such that the remaining aspartate unit can cyclize to a succinimide unit during the polymerization. Cations which have at least 50% dissociation in this manner under the given drying conditions are considered volatile or heat-decomposable and cations which do not dissociate at least 50% are considered non-volatile or non-heat decomposable.
In the present invention, some elements of the conventional, enzymatic processes for production of aspartic acid can be adapted for producing monomers useful in the invention. The production of the comonomer mixture, however, is a novel aspect. The method involves providing an intimate solution of an aspartate of a non-volatile cation and an aspartate of a volatile cation. By the term aspartate is meant an aspartic acid residue, either as a monomer or as a polymerized or copolymerized unit having its carboxyl group in ionic form associated with a cation, i.e., as xe2x80x94COOxe2x88x92. Specifically, for example, an ammonium aspartate solution can be titrated with NaOH to a fractional molar equivalence of a sodium salt of aspartate and an ammonium salt of aspartate. This comonomeric solution is then dried to produce a comonomer mixture of a partial sodium salt of aspartic acid and free aspartic acid. By free aspartic acid is meant aspartic acid or a polymerized or copolymerized aspartic acid residue having its carboxyl group not in ionic form, i.e., xe2x80x94COOH. Because the dried comonomer mixture is prepared from the novel intimate solution of comonomers, an intimate dried mixture of these comonomers is obtained. Although not intending to be bound by this theory, it is believed that the mixture is intimate to the extent of exhibiting a salt lattice structure of the aspartate with the aspartic acid. It is possible for the dried comonomeric composition to also contain some residual ammonium aspartate, but in very small amounts, e.g., not exceeding 5% by weight, preferably not exceeding 2% by weight.
In effect, the aspartate of the volatile cation (e.g. ammonium) when dried from aqueous solution, is largely converted to powdered or crystalline aspartic acid. This is due to the loss of the decomposable cation, e.g., ammonia, as a vapor upon drying, with accompanying lowering of the pH of the evaporating solution as ammonia leaves the solution, for example, as a result of the following equilibrium being pulled to the left:
↑NH3⇄NH3+H2O⇄NH4OH⇄NH4++OHxe2x88x92. 
The sodium ion, on the other hand, has no significant vapor phase during drying and remains in the dried salt as a counter ion to aspartate monomers. Thus, the relative proportions of the comonomers, monosodium aspartate and aspartic acid, is set by the relative molar amounts of ammonium aspartate in solution and the NaOH added to the solution prior to drying.
The dried comonomer mixture is a clear, glassy solid if drying occurs in vacuo or in an oxygen-depleted atmosphere. In the presence of atmospheric oxygen, the dried comonomer preparation has a pale yellow, glassy appearance.
The comonomer composition of the present invention may also be prepared via nonenzymatic, chemical production of solutions of ammonium aspartate. For example, maleic acid plus ammonia in water plus heating, preferably at an elevated pressure, may produce ammonium aspartate in solution. Typically, temperatures of 80 to 160xc2x0 C., preferably 120 to 160xc2x0 C. and a pressure of up to about 120 psi can be used, although other conditions may be useful depending on the particular circumstances. Upon addition of the desired amount of NaOH, this solution is dried to form the comonomer composition containing the mixture of the sodium aspartate salt and aspartic acid.
The comonomeric composition may also be obtained via coprecipitation from solution. For example, addition of a hydrophobe or downward adjustment of pH may lead to coprecipitation of the monomers. These may then be isolated, for example by filtration, for use in the production of the imide-containing polymers.
Also included are methods in which maleic acid plus ammonia plus soluble, nonalkali as well as alkali, cationic salts are used to internally generate a combination of aspartic acid and monosodium aspartate comonomers for thermal polymerization to produce water-soluble, imide containing copolymers.
Upon polymerization, for example by thermal polycondensation, of the comonomer composition, any residual ammonia of the ammonium salt is further driven off as a vapor. The resulting product is a copolymer of sodium aspartate and succinimide units. Due to the novel comonomer dry mixture used to prepare this copolymer, a true copolymer is obtained with a significant amount of both of these amide and imide units. For example, it is preferred that such units are provided in the copolymer in a molar ratio of from 1:10 to 10:1, more preferably 1:5 to 5:1, particularly preferably 14 to 4:1 or at about 1:1. Exemplification of the ratios achievable is provided in the following Table 1.
These copolymers exhibit advantageous properties, particularly advantageous water solubility properties, which makes them economically and ecologically advantageous for use in many applications. For example, they can provide biodegradable polymers and polymers which can otherwise be adjusted to suit particular uses. Table 2 exemplifies some of the advantageous solubility properties of copolymers of the invention.
Additional comonomers may be added prior to the drying of the comonomer solution step to provide comonomeric feedstock for terpolymers and high polymers of thermally condensed polyamino acids. In particular, the amino acids lysine and glutamate and salts thereof may be used. These can impart further water-solubility to the product imide-containing polymers. Moreover, other difunctional and multifunctional monomers such as aminocaproic acid and ornithine, as well as the other common amino acids including but not limited to alanine, glycine, leucine, isoleucine, methionine which can form a sulfoxide by oxidation of the thioether, and theronine; sugar-acids such as glucuronic acid; other hydroxyl-containing carboxylates such as citric acid and malonic acids; and other like molecules, are additional comonomers that would co-condense in the production of the imide-containing polyamino acids and may be useful to provide aqueous solubility and other useful properties to the imide-containing polyamino acids.
Additional preferred comonomers include, but are not limited to caprolactam; caprolactone; glutamine; arginine; asparagine, which is inherently present in the product, in accordance with the present invention, in an amount of from 0 to 15%; and cystine, which preferably forms a disulfide which can be further subjected to reductive cleavage to yield two mercaptans, which mercaptans are available for further derivatization or oxidative cleavage to form a sulfonate. Further, additional comonomers include, but are not limited, an aminosugar, glutamine, and chitin, chitosan, at a weight average molecular weight ranging from an oligomer to 1,000,000 including all increments within the above range. The term xe2x80x9coligomerxe2x80x9d as used in the present application denotes a material with a degree of polymerization (DP) between 10 and 1000. Further comonomers include but are not limited, a polysaccharide ranging in weight average molecular weight from that of an oligomer to that of a naturally occurring polysaccharide, including all increments within the above range.
Accordingly, it is one object of the present invention to provide novel comonomeric compositions. It is another object of the present invention to provide methods of preparation of the novel comonomeric compositions. It is another object of the present invention to provide uses of the novel comonomeric compositions, particularly for copolymerization to prepare novel copolymers. It is another object of the present invention to provide novel imide-containing polyamino acids. It is another object of the present invention to provide methods of synthesis of the imide-containing polyamino acids. It is another object of the present invention to provide methods of commercial manufacture of the imide-containing polyamino acids. It is another object of the present invention to provide methods of using, including commercial uses, of the imide-containing polyamino acids. This exemplification of objects of the invention is not a limitation and other objects and advantages of the invention are either explicitly or implicitly included in the disclosure as a whole, taking the knowledge of one of ordinary skills in the art into consideration.
Comonomeric compositions. The comonomeric compositions of the present invention can be prepared via the intimate solutions described above.
To prepare the starting solutions of aspartic acid and/or ammonium aspartate any current commercial process may be used. For example, dried powders or crystals of L-aspartic acid may be prepared by acid-precipitation of ammonium aspartate solutions such as occur as an intermediate stage of the immobilized enzyme route to aspartic acid.
Alternatively, aspartic acid for use in the present invention may be prepared chemically via addition of ammonia to maleic acid or fumaric acid plus heat, followed by acid precipitation of the aspartic acid zwitterion. Accordingly, either L-aspartic acid or D-aspartic acid may be used, or mixtures of L,D-aspartic acid may be used in this invention.
A novel and preferred method of preparation of the composition of comonomeric salts of the present invention is to add alkali to a concentrated solution of ammonium aspartate, where the solution of ammonium aspartate is prepared by any of the prior routes for production of aspartic acid. Specifically, stoichiometric, substoichiometric, or suprastoichiometric amounts of one or more alkali compounds relative to the molar amounts of ammonium aspartate, either diammonium or monoammonium, may be added. The solutions are then dried by any method, preferably at a temperature of from 80 to 140xc2x0 C., more preferably oven-dried at 120xc2x0 C., to form the partial sodium salt of aspartate and aspartic acid, although residual ammonium aspartate may also be present. Drying could also be conducted by spray drying, lyophilization, vacuum methods or forced air. The drying can be halted at a time before polymerization of the comonomers begins. However, it is also possible to continue the drying step after the comonomers are formed to proceed with the copolymerization thereof, as discussed below, in situ.
During the drying step, the ammonia is largely released to the atmosphere, which ammonia gas may be scrubbed by passage through an acidified, cool-water trap. The ammonium aspartate thus reverts to the aspartic acid form. The sodium hydroxide acts to neutralize some of the aspartic acid upon drying. The sodium ion, having no significant vapor pressure, remains in the comonomeric salt composition of the present invention in the form of monosodium aspartate.
If the drying step is accomplished with heating in vacuo, by lyophilization, or with heating in an inert, oxygen-depleted atmosphere such as nitrogen gas, the resultant comonomeric salt of the present invention is a colorless, clear, glassy solid that may be obtained in various forms ranging from a solid puck to glassy particles to shards to powders.
Another preferred method of preparation of the comonomeric salts of the present invention is to mix stoichiometric, substoichiometric, suprastoichiometric solutions of sodium aspartate with a solution of ammonium aspartate. For example, dry or powdered aspartic acid may be solubilized by titration with a minimal amount of NaOH, just sufficient to render the aspartic acid into solution. Alternatively, the NaOH may be added in an excess, for example sufficient to provide two sodium ions per molecule of aspartic acid. Next, the two solutions are mixed, with addition of enough of one with the other to provide a combined solutions containing the targeted molar ratio of ammonium versus sodium aspartate, in either case either the di- or mono-ammonium or di- or monosodium salts. The drying is then conducted as described above or by any other conventional means, leaving the resulting comonomer preparation of the present invention.
In any of the above methods, the amounts of the aspartic acid and aspartate salts used are provided to reflect the desired ratio of amide and imide units in the eventual copolymer. The desired ratio may be selected based on the properties desired, e.g., a higher ratio of amide (aspartate) units in the copolymer will provide it greater solubility. Thus, e.g., a molar ratio of from 1:10 to 10:1, more preferably 1:4 to 4:1, particularly about 1:1, may be used.
The amide-generating or imide-generating monomers are not limited to ones having sodium and ammonium cations, respectively; other cations may be used in a manner analogous to that described above. As the amide-generating cations may be used those which form aspartate salts wherein the cation is non-volatile or not heat decomposable under the conditions for drying to the comonomer mixture. Preferred, therefore, are cations which exhibit no significant vapor pressure at 120xc2x0 C. Representative examples include any metallic cation, such as alkali metal, alkaline earth metals or transition metals. Preferably the cations are alkali or alkaline earth metals, particularly Na, Mg, K, Ca, Rb, Sr, Cs and Ba, with sodium, magnesium, potassium and calcium, particularly sodium, being preferred alkali metals and alkaline earth metals. As the imide-generating cations may be used those which form aspartate salts which are volatile or heat decomposable under the conditions for drying to the comonomer mixture. Preferred, therefore, are cations that volatilize or are otherwise dissipated at 120xc2x0 C. Representative examples include ammonium and other amines which provide counterions to aspartate carboxylic groups in solution, e.g., ethanolamine, propanolamine and monoaminobutane.
Comonomers in addition to the amide-generating and imide-generating aspartates may be used in the preparation of comonomer compositions for the production of imide-containing polyamino acids, and analogous methods to those described above using such other monomers are included in the invention. Use of such additional comonomers results in terpolymers or higher polymers. These further comonomers may be selected from among any comonomers which copolymerize and do not interfere with formation of the amide/imide copolymer units. Many useful comonomers are conventionally known and are included here, for example, other amino acids, e.g., any natural or modified amino acids as long as they contain at least one amino group and at least one carboxylic group free for polymerization and salts thereof.
The amount of the additional comonomer used is preferably in the range of 10- to 50% weight based on the total weight of the amide- and imide-generating comonomers.
An example of an additional comonomer is monosodium glutamate. Monosodium glutamate in dry form or as a solution may be added to a solution of ammonium aspartate, mixed to make a combined solution, then dried by any conventional means to produce a dried comonomer composition of aspartic acid and monosodium glutamate. The composition may also contain sodium aspartate, glutamic acid, or a combination of these comonomers.
Another preferred comonomer is lysine. Lysine, most preferably as the free base, and preferably having few or no counterions, such as chloride, associated with the amine groups of lysine, may be added in dry form or as a solution to a solution of ammonium aspartate, mixed to make a combined solution, then dried by any conventional means to produce a dried comonomer composition of aspartic acid and lysine. The composition may also contain sodium aspartate, glutamic acid, sodium glutamate, or a combination of these comonomers. Lysine may also be added as the chloride salt, lysine-HCl, but this is not particularly preferred, as the chloride may form counterions with free amino groups of the amino acids upon drying, blocking them from participating in the thermal polycondensation reaction to form the ultimate products, the imide-containing polyamino acids.
Lysine in the free-base form, which is prepared commercially as the zwitterion, when incorporated into the comonomer composition of the present invention, acts to extend the molecular size of the imide-containing polyamino acid products, presumably trough chain-extension and crosslinking. Similarly, other diamino or polyamino monomeric coreactants may be used for this purpose. For example, ornithine may be used, as may aminocaproic acid, diaminohexane, diaminobutane and diaminopentane.
In all cases, the L-, D-, or mixed L-,D-isomers of the monomeric amino acids and other comonomers may be used.
In a separate embodiment for providing a comonomer mixture useful for obtaining imide-containing polyamino acids, sodium bicarbonate or other carbonate ion-providing compounds can be used. The water of condensation creates a vapor phase during the polymerization of aspartic acid. In the presence of sodium bicarbonate, bicarbonate anion can enter a transitory aqueous state, with sodium cation also solubilized momentarily. The bicarbonate decomposes in the presence of heat and water vapor to release CO2 and water, further stirring the admixture through gaseous emission. The sodium can become a counterion to some of the aspartic residues in the form of monosodium aspartate, thus generating an intimate mixture of aspartic acid and monosodium aspartate comonomers. Upon thermal polymerization, this intimate mixture converts to the copolymer of aspartate and succinimide as further discussed below.
Manufacture of the Imide-Containing Polyamino Acids. The novel polymeric molecules of the present invention may be produced via methods analogous to those described in the prior art for manufacture, including commercial manufacture, of the homopolymers, polysuccinimide and polyaspartate, except of course using the comonomer compositions according to the invention. Accordingly, the molecules of the present invention may be manufactured by the approaches exemplified in Table 3, which includes relevant prior art references, incorporated herein in their entirety by reference. In one preferred embodiment, the comonomer mixture is heated by a thermal polycondensation method. Although the polymerization time and temperature will depend on the comonomer mixture used and the result desired, the polymerization can preferably be conducted at a temperature of from 140 to 350xc2x0 C., more preferably 160 to 280xc2x0 C., particularly 200 to 240xc2x0 C., for preferably 1 minute to 72 hours, more preferably 5 minutes to 8 hours, to form the copolymers. In one embodiment of the preparation, a thin film evaporator may be used to provide a short time (e.g., as little as 5 minutes) for complete conversion of the monomers to the polymer due to the efficiency of heat exchange and removal of water of condensation.
The copolymers may be formed in a large range of molecular weights. In one embodiment, the copolymers may exhibit a gel permeation molecular weight of from 300 to 5,000 daltons, particular 500 to 3,000 daltons. A higher ration of succinimide units will generally result in a higher molecular weight copolymer. In other embodiments the copolymer may be polymerized to an extent to provide a molecular weight of 100,000 or higher. The molecular weight of the copolymer may be increased by including a polyamine (including diamines) as an additional comonomer, see the description regarding comonomers above. Suitable diamines and polyamines include aliphatic diamine, arylaliphatic diamines, as well as triamino, tetramino and polyamino compounds, such as polyoxylakylene triamine, polyoxyalkylene diamine, triethylene tetraamine and tetraethylene pentamine. Such polyoxylalkylene amines are available, for example, as JEFFAMINES(copyright) from Huntsman Specialty Chemicals and as STARBURST(copyright) dendrimers from Dendritech, Inc. The JEFFAMINES(copyright) typically contain ethylene and/or propylene oxide units and have molecular weights ranging from 600 to 5,000. Preferred polyamines are diaminopropane, diaminobutane, diaminopentane, diaminohexane, diaminoheptane, diaminoctane, ornithine, ornithine methyl ester, lysine, lysine methyl ester, spermine and spermidine. Particularly preferred diamines include diaminobutane, diaminopropane, diaminohexane and lysine methyl ester.
Typically, the polyamine is incorporated in a monomer mixture of polyamine and monosodium aspartate in an amount of 1 to 50 mole %, preferably 5 to 15 mole %, based on the total moles of polyamine and salt of aspartic acid in the monomer mixture. By including a polyamine in the monomer mixture it is possible to increase the molecular weight of the resulting poly(aspartate, succinimide) to 100,000 daltons and higher as measured by gel permeation.
In another embodiment, the present method may be carried out by polymerizing the comonomer mixture of the invention in the presence of a preformed polyaspartate. The preformed polyaspartate may be that prepared by a process analogous to that described in U.S. Pat. No. 5,981,691 or that prepared by some other conventional polymerization of aspartic acid or aspartates followed by hydrolysis. Typically, the preformed polyaspartate will have a gel permeation molecular weight of 1000 to 100,000, preferably 2000 to 30,000 daltons. The preformed polyaspartate is usually included in the polymerization in an amount of 25 to 95 mole %, preferably 50 to 90 mole %, based on the total moles of residues (monomer units) of the copolymer.
In a preferred embodiment the polymerization is performed in a solvent in which the formed copolymer of the present invention is soluble or in a solvent which can swell the formed copolymer thereby achieving greater molecular weight in the range of 50,000 to 1,000,000 weight average molecular weight (Mw), including any increments within the above range. Selection of such solvents is known in the art; such selection is made by knowledge of the solvent-solute interaction. In addition, solubility parameters are useful in selecting a solvent. The method for selecting a solvent is described in Kirk-Othmer, Concise Encyclopedia of Chemical Technology, A Wiley-Interscience Publication, John Wiley and Sons, New York (1985), Chapter on xe2x80x9cSolventsxe2x80x9d pages 1091-1092, which chapter is incorporated herein by reference in its entirety. In an alternative route a high molecular weight polysuccinimide (PSI) is prepared which is subsequently undergone controlled hydrolysis and derivatization via the use of solvents which can swell the polysuccinimide. In another alternative a polyfunctional amine, a polyfunctional acid or a polyfunctional hydroxyl compound is included in the monomer mixture to form a dimer, a trimer or a star copolymer, including a diamine, a triamine, trimellitic acid, or a carbohydrate such as trehalose or a maltose. In a further preferred embodiment the polymerization is performed using pyrophosphoric acid, in an amount of 20-50% by weight based on monomer weight, thus resulting in a copolymer with reduced color and increased molecular weight.
By the use of preformed polyaspartates or by other methods, copolymers according to the invention can be provided having at least a partially block copolymer structure. Additionally, graft copolymers can be provided according to known methods.
The copolymers of the invention can exhibit a linear structure or branched structure, including three-dimensional structuring. Crosslinking of the copolymers according to known methods can also be conducted. Also, a variety of terminal groups known in the art can be provided on the copolymers.
Uses of the Imide-Containing Polyamino Acids. The novel molecules of the present invention may be used in a manner analogous to that described in the prior art for possible uses of polysuccinimides and polyaspartates, including described commercial uses. Accordingly, the molecules of the past invention, i.e., including the described copolymers of aspartate and succinimide (i.e., the imide-containing polyamino acids) and the derivatives thereof discussed below, may be used as summarized in Table 4, which includes the relevant prior art references, incorporated herein in their entirety by reference.
Preferred but non-limiting uses of the copolymers or the below-discussed derivatives thereof include, use as: detergent, e.g., liquid or powdered, additives; cosmetic additives, such as softeners or emollients; hair conditioners or shampoo additives, dispersants in cementitious materials; active agents in coatings, crosslinkers or binders; anti-scalants; corrosion inhibitors; adhesives; strengthener or binder agents for paper products; and gelling or thickening agents.
Derivatization. In addition to the uses as described above, the polyamino acids of the present invention preferably may be used in the synthesis of advanced derivatives. That is, advanced derivatives may be prepared via nucleophilic addition of nucleophilic group-containing compounds, such as amine or xe2x80x94OH group-containing compounds, to the imide residues of the imide-containing polyamino acids of the present invention. These pendant compounds become attached to the polymer backbone, for example, via amide bonds for the amine compounds or via ester bonds for the xe2x80x94OH group-containing compounds.
Preferably, the derivatization is accomplished in an aqueous solution of the imide-containing polyamino acids. Particularly preferred are aqueous solutions adjusted to the nucleophilic pH range. For example, a preferred pH range is 8 to 12. Particularly preferred is the pH range of 10 to 11. The derivatization can be conducted at a wide range of temperatures with 5 to 90xc2x0 C., more preferably 20 to 60xc2x0 C., particularly 30 to 50xc2x0 C., being preferred. The amount of the succinimide units derivatized can vary from 1 to all of such units. Some nucleophilic add-ons may be reacted from an emulsion.
Although water is the preferred solvent, organic solvents may be used as well, particularly in the case in which the imide-containing polyamino acids are partially or completely insoluble in water. Preferred polar solvents in these cases are alcohols, particularly isopropanol. Preferred nonpolar solvents are dimethyl formamide, dichloromethane, and particularly N-methyl-pyrrolidone. In some cases, miscible solutions of more than one solvent, including water, may be preferred for derivatization of particular imide-containing polyamino acids.
If the preferred nucleophile itself is not very water-soluble, it may be added as an emulsion to the solution of the imide-containing polyamino acid. For example, the hair-conditioning agent trimethylsilylamodimethicone, is such a water-insoluble nucleophile that many be added as an emulsion to the water-soluble, imide-containing polyamino acid.
Particularly preferred examples of amine compounds for making the derivatives include monoamino polyoxylakylenes, monoamino siloxanes, monoamino phosphonates, monoamino sulfonates, ethanolamine, and other amino alcohols. These amine compounds may be added at one imide residue per polymer molecule, at every imide residue per molecule, or at any other percentage of the imide residues per polymer molecule.
Similarly, amino acids in general also may be added to the imide-containing polymers of the present invention via nucleophilic addition. For example, preferred additional amino acids to be added via this approach include: leucine, to provide hydrophobic character; serine, to provide a pendant alcoholic group; dihydroxyphenylalanine, to provide catecholic character; phosphoserine, to provide a stronger anionic pendant group, to provide intermediate hydrophobicity, etc. Other amino acids can be added to extend the molecules, for example preferably aminocaproic acid and caprolactam. Thus, any and all amino acids may be added to the imide-containing polyamino acids via nucleophilic addition, for the purposes of adding functional group characteristics ranging from hydrophobic, to nonionic, to anionic, to cationic.
In a preferred embodiment the imide-containing polyamino acid is derivatized by an amine. By way of non-limiting examples an imidazoline or an amino pyridine may be added to the imide-containing polyamino acid to form an anticorrosive polymer via oxidation to the N-oxide or quaternization, formed from the ring opening with amines that have a tertiary nitrogen. Such a quaternary compound is useful as a coagulant or as a biocide. Further, a polyamine, such as a diamine, a triamine, a protein, a peptide, a gelatin, chitin, lysine, ornithine, or a melamine, can be used to crosslink the imide-containing polyamino acid to achieve higher molecular weight, gel, or to provide additional sites for further reactions. An example of the latter is to open the succinimide ring with an aminoalcohol, such as a diethanolamine, to provide a polyfunctional OH group-containing resin to further react in a powder coating application. A further example is to open all the succinimide rings with sufficient diamine, such as hexamethylene diamine, so that no crosslinking can occur but that each amide formed now has an amine group at the end. Thus, chemistry can be performed on that amine group, such as a reaction with a polyfunctional isocyanate to chain extend the imide-containing polyamino acid or to form a crosslinked gel. An amino ethoxylate can be used to form a polymer with a long chain ethoxylate to be used as a thickener or as a dispersant depending upon the molecular weight (Mw) of the starting resin. Also, an aminoethoxylate containing a hydrophobic end group can be used to form a rheology modifier or an associative thickener. An additional amino functional material can be used to react in a nucleophilic addition with the imide-containing polyamino acid such as: an allyl amine to give free radical crosslinking functionality for ultraviolet (UV) or electron beam (EB) curing of a coating. Further, amino polybutadiene and an amino terminated fatty olefin can be used in a nucleophilic addition with the imide-containing polyamino acid which could achieve the same result as an allyl amine and in addition be able to crosslink by an oxidative cure mechanism. Further, an amino-aromatic compound, such as aniline or a substituted aniline can be used in the nucleophilic addition in accordance with the present invention.
Another preferred embodiment of production of the advanced derivatives is to add OH-containing molecules to the imide residues of the imide-containing polyamino acids via nucleophilic addition under mildly alkaline aqueous conditions with or without mild heating. These pendant compounds become attached to the polymer backbone via ester linkages.
Preferred examples of the OH-containing compounds for addition to the polymer backbones include monomeric carbohydrates and disaccharides such as glucose, galactose, mannose, lactose, sucrose, and others. In addition, polysaccharides such as cellulose, starch, amylose, as well as their oligosaccharide fragments, may be reacted with the imide-containing polyamino acids.
In another preferred embodiment to the imide-containing polyamino acid is derivetized by an OH-group containing material. Thus, many of the above functionalities can be added to the succinimide ring via the use of an OH terminated material using, for example, a tertiary amine as a catalyst. These would include compounds, such as a polyethoxylate and a hydrophobe terminated ethoxylate. Some additional materials which can be attached via the succinimide ring to form an ester include, but are not limited to: a starch; a dextrin; a cellulose, to preferably form a highly water swellable material, which finds use as a liquid absorbent material for hygiene items such as a diaper, for holding water in an agricultural application, etc; hydroxyl acrylate and hydroxyl methacrylate, preferably for producing polymerizable oligomers. OH-containing acids can be used to provide additional COOH/COOxe2x80x94 functionality further out from the backbone which could be used as a dispersant or a thickener depending upon the molecular weight (Mw) of the material formed. Non-limiting examples include, a phenolic, such as a lignin, can be reacted with the succinimide ring.
In an additional preferred embodiment to the imide-containing polyamino acid is derivetized by a SH-group containing material. Thus, the SH group can be used in a similar fashion to the OH group. In fact the ring opening reaction is more facile than with the OH group as the SH group has a lower pK and does not require a catalyst. However, although the absence of a catalyst is preferred, the use of a catalyst is not excluded in the ring opening reaction described above, in accordance with the present invention. Any mercaptan containing compound should be amenable to opening up the ring and forming a thioester.
In each preferred embodiment in which the succinimide residues are derivatized with added functional molecules, it is possible to derivatize all of the succinimide residues per molecule of the imide-containing polyamino acids. It is also possible to derivatize as few of the succinimide residue per molecule, on average. For example, it is possible to derivatize from 1% to 100% of the available succinimide residues in a solution of the imide-containing polyamino acids. Preferably, from 5% to 80% would be derivatized; more preferably from 10% to 60%; most preferably from 20% to 50%.
In addition, it is possible to add the nucleophile derivatizing molecules to a solution of the imide-containing polyamino acids; or alternatively, it is possible to add the imide-containing polyamino acids to a solution of the nucleophile derivatizing molecules. For example, if there is an excess of nucleophilic amines left free in solution due to a limitation of available succinimide residues for whatever reason, it is possible to add more of the imide-containing polyamino acid until all of the nucleophilic amines attach covalently to the polymer.
The drivatized copolymers are useful in a manner analogous to the copolymers, as described above, but exhibit the modified properties imparted by the added pendant groups.
Additional uses of the derivatized copolymers by nucleophilic addition include but are not limited to additives in detergents, such as for oily soil, anti-deposition, cleaning, soil release, dispersancy, dye transfer, thickener, tablet excipient, wetting agent, sticker, and crystal inhibition; as dispersant additives, such as in ceramics, minerals and fillers; as thickeners, such as rheology modifiers; superabsorbents; humectants; and coagulants; as additives in agricultural applications, such as moisture retention agent, controlled release and as coatings for seeds; for personal care products, such as additives for hair care, and face and skin creams or lotions; in leather applications, such as syntan and fat liquid/lubricant; in plastics, such as plasticizers, preferably for vinyl alcohol or vinyl esters, compatibilizing agents for composite materials; in biomedical applications, such as coatings, arrays, elisa coatings, enzyme linked, tissue culture plates, tissue preservation; in pharmaceutical applications, such as controlled release, capsule, and excipients for tablets such as disintegrent, coating and binder; in food application such as ice formation inhibitors, preferably in ice cream; in coatings applications, such as rheology modifier, crosslinking agent, water removal agent, binder and as ultraviolet radiation curable materials; as ion exchange resin, preferably in fibers, such as providing dye receptor sites and modified cellulose fibers; in packaging, such as water soluble package; in composites of cellulose materials; as adhesives; and as surfactants.